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Egyptian Journal of Biochemistry and Molecular Biology

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Dexamethasone improves the responsiveness of hepatoma cells for both free and solvent containing paclitaxel in vitro

Samar S. Alkafaas, Thoria Diab, Thanaa Shalaby, Mohamed Hessien

Abstract


This work was designated to explore the effect of glucocorticoid (dexamethasone) on the responsiveness of hepatoma cells to Paclitaxel (PTX) and the expression of Taxol resistance gene (Txr1) and the paclitaxel metabolizing genes. Hepatocellular carcinoma cells (HepG2) were treated with standard paclitaxel (PTX) or solvent containing paclitaxel (Taxol) in the presence or absence of dexamethasone (DEX). Cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Also, total RNA was isolated, reverse transcribed and used to determine the expression levels of Txr1, CYP 3A4, and CYP2C8 genes.

Initially, HepG2 cells were more resistant to PTX than Taxol. Also, cells became more responsive to the standard PTX and Taxol in the presence of DEX, where the IC50 values decreased from 42.5 μg/ml to 13.07 μg/ml and from 6.5 μg/ml to 3.6 μg/ml, respectively. Apoptosis was the main mechanism of cytotoxicity in cells treated with PTX or Taxol. The involvement of DEX, however, decreased the percent of apoptotic cells. Moreover, the expression of Txr1 decreased by 18% and 35% in cells cotreated with PTX+DEX or Taxol+DEX. In parallel, the expression of paclitaxel metabolizing genes (CYP3A4 and CYP2C8) was increased compared to DEX free cells. This in vitro study reports the associations between the enhanced responsiveness of hepatoma cells to paclitaxel or Taxol in presence of dexamethasone, associated with a decrease in drug resistance and upregulation of the paclitaxel metabolizing genes.

Keywords: Liver cancer, Paclitaxel nanoparticles, Taxol resistance gene, CYPs




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